Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance

Glioblastoma is the most common form of primary malignant brain tumor in adults and one of the most lethal human cancers, with high recurrence and therapy resistance. Glioblastoma cells display extensive genetic and cellular heterogeneity, which precludes a unique and common therapeutic approach. Th...

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Authors: Zarzuela, Laura, Durán, Raúl V, Tomé, Mercedes
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/400243
Online Access:http://hdl.handle.net/10261/400243
https://api.elsevier.com/content/abstract/scopus_id/85180913283
Access Level:Open access
Keyword:Cell signaling
Glioblastoma
Metabolism
Temozolomide
Therapy resistance
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spelling Metabolism and signaling crosstalk in glioblastoma progression and therapy resistanceZarzuela, LauraDurán, Raúl VTomé, MercedesCell signalingGlioblastomaMetabolismTemozolomideTherapy resistanceGlioblastoma is the most common form of primary malignant brain tumor in adults and one of the most lethal human cancers, with high recurrence and therapy resistance. Glioblastoma cells display extensive genetic and cellular heterogeneity, which precludes a unique and common therapeutic approach. The standard of care in glioblastoma patients includes surgery followed by radiotherapy plus concomitant temozolomide. As in many other cancers, cell signaling is deeply affected due to mutations or alterations in the so-called molecular drivers. Moreover, glioblastoma cells undergo metabolic adaptations to meet the new demands in terms of energy and building blocks, with an increasing amount of evidence connecting metabolic transformation and cell signaling deregulation in this type of aggressive brain tumor. In this review, we summarize some of the most common alterations both in cell signaling and metabolism in glioblastoma, presenting an integrative discussion about how they contribute to therapy resistance. Furthermore, this review aims at providing a comprehensive overview of the state-of-the-art of therapeutic approaches and clinical trials exploiting signaling and metabolism in glioblastoma.RVD and MT were supported by Spanish Ministry of Science and Innovation, Spanish Research Agency, and European Regional Development Fund (project PID2021-124251OB-I00 funded by MCIN/AEI/10.13039/501100011033/FEDER, UE). LZ was supported by FPU fellowship (FPU19/04914) from the Spanish Ministry of Universities. Figures created with BioRender.com.Peer reviewedJohn Wiley & SonsAgencia Estatal de Investigación (España)Ministerio de Ciencia e Innovación (España)European CommissionMinisterio de Universidades (España)Durán, Raúl V. [0000-0002-2249-9215]Tomé, Mercedes [0000-0001-8682-1800]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/400243https://api.elsevier.com/content/abstract/scopus_id/85180913283reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-124251OB-I00https://doi.org/10.1002/1878-0261.13571Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4002432026-05-22T06:33:51Z
dc.title.none.fl_str_mv Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance
title Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance
spellingShingle Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance
Zarzuela, Laura
Cell signaling
Glioblastoma
Metabolism
Temozolomide
Therapy resistance
title_short Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance
title_full Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance
title_fullStr Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance
title_full_unstemmed Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance
title_sort Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance
dc.creator.none.fl_str_mv Zarzuela, Laura
Durán, Raúl V
Tomé, Mercedes
author Zarzuela, Laura
author_facet Zarzuela, Laura
Durán, Raúl V
Tomé, Mercedes
author_role author
author2 Durán, Raúl V
Tomé, Mercedes
author2_role author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Ministerio de Ciencia e Innovación (España)
European Commission
Ministerio de Universidades (España)
Durán, Raúl V. [0000-0002-2249-9215]
Tomé, Mercedes [0000-0001-8682-1800]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cell signaling
Glioblastoma
Metabolism
Temozolomide
Therapy resistance
topic Cell signaling
Glioblastoma
Metabolism
Temozolomide
Therapy resistance
description Glioblastoma is the most common form of primary malignant brain tumor in adults and one of the most lethal human cancers, with high recurrence and therapy resistance. Glioblastoma cells display extensive genetic and cellular heterogeneity, which precludes a unique and common therapeutic approach. The standard of care in glioblastoma patients includes surgery followed by radiotherapy plus concomitant temozolomide. As in many other cancers, cell signaling is deeply affected due to mutations or alterations in the so-called molecular drivers. Moreover, glioblastoma cells undergo metabolic adaptations to meet the new demands in terms of energy and building blocks, with an increasing amount of evidence connecting metabolic transformation and cell signaling deregulation in this type of aggressive brain tumor. In this review, we summarize some of the most common alterations both in cell signaling and metabolism in glioblastoma, presenting an integrative discussion about how they contribute to therapy resistance. Furthermore, this review aims at providing a comprehensive overview of the state-of-the-art of therapeutic approaches and clinical trials exploiting signaling and metabolism in glioblastoma.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/400243
https://api.elsevier.com/content/abstract/scopus_id/85180913283
url http://hdl.handle.net/10261/400243
https://api.elsevier.com/content/abstract/scopus_id/85180913283
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-124251OB-I00
https://doi.org/10.1002/1878-0261.13571
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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